The never-ending story of the fight against tuberculosis: from Koch’s bacillus to global control programs


History of tuberculosis
Bacille Calmette Guerìn
Mycobacterium tuberculosis
tuberculosis control strategy


Tuberculosis (TB) is one of the oldest diseases known to affect humanity, and is still a major public health problem. It is caused by the bacillus Mycobacterium tuberculosis (MT), which was first isolated in 1882 by Robert Koch. In 1882, Franz Zhiel and Fredrich Neelson stained MT with the acidalcohol-fast bacillus, a technique still used today. Until the 1950s, X rays were used as a cheap method of diagnostic screening  together with the tuberculin skin sensitivity test. In the diagnosis and treatment of TB, an important role was also played by surgery, such as artificial intrapleural pneumothorax, though this approach often led to complications, such as empyema. The late 19th century saw the introduction of the tuberculosis sanatorium, which proved to be  one of the first useful measures against TB. Subsequently, Albert Calmette and Camille Guérin used a non-virulent MT strain to produce a live attenuated vaccine. In the 1980s and 1990s, the incidence of tuberculosis surged as a major opportunistic infection in people with HIV infection and AIDS; for this reason, a combined strategy based on improving drug treatment, diagnostic instruments and prevention was needed in order to better control the disease, as recommended by the World Health Organization (WHO). Since the beginning of the 21st century, new prophylactic and therapeutic vaccines have been tested in order to better control the pulmonary form of TB.


Saeed B.W. Malignant tuberculosis. (J Ayub Med Coll Abbottabad,2006), 18(3):1-2. 2.

Nasyr Puyan. The fight against tuberculosis, the loathsome killer. Int.J.Curr.Microbiol App Sci. 2015; 4(1): 380-393.

Keal JL, Davies PD. Tuberculosis: a forgotten plague? (J R Soc Med, 2011 May;104(5):182 4. doi: 10.1258/jrsm.2011.100384

Tanday S. Will we ever eliminate tuberculosis, the voiceless disease? Lancet Respir Med. 2017 Mar 15. pii: S2213-2600(17)30080-2. doi: 10.1016/S2213-2600(17)30080-2.

Global Tuberculosis Report 2016 - World Health Organization. Available from: Last access: 15th October 2017

Frith J. History of tuberculosis Part 2 - The sanatoria and the discoveries of the tubercle Bacillus. Journal of military and veterans’ health. 2014; 22:2.

Chalke HD. The impact of tuberculosis on history, literature and art. Medical History. 1962; 6:301–18.

Barberis I, Bragazzi NL, Galluzzo L, Martini M. The history of tuberculosis: from the first historical records to the isolation of Koch’s bacillus. J Prev Med Hyg. 2017; 58(1):E9-E12.

Weigert C. Färbung der Bacterien mit Anilinfarben. Universitäte at Breslau, Breslau, 1875

Ziehl F. Zur Färbung des tuberkelbacillus. Dtsch Med Wochenschr. 1882; 8: 451.

Cambau E, Drancourt M. Steps towards the discovery of Mycobacterium tuberculosis by Robert Koch, 1882. Clin Microbiol Infect. 2014; 20(3):196-201.

Marten B. A New Theory of Consumptions—More Especially a Phthisis or Consumption of the Lungs. London, T. Knaplock, 1720.

Daniel TM. The history of tuberculosis. Resp Med. 2006; 100: 1862-1870. Available at: http://www.

Herzog H. History of tuberculosis. Respiration. 1998; 65: 5-15. Available at : Article/PDF/29220.

Sakula A. Robert Koch: centenary of the discovery of the tubercle bacillus, 1882. Thorax. 1982; 37: 246251. Available at :

Daniel TM. Pioneers in Medicine and their Impact on Tuberculosis. University of Rochester Press, 2000: pp 74-76, 179.

Garrison F H. An Introduction to the History of Medicine. Philadelphia & London: W B Saunders & Co., 1921: pp 578-590, 721.

Boire NA, Riede VAA, Parrish NM, Riedel S. Tuberculosis: from an untreatable disease in antiquity to an untreatable disease in modern times. J Anc Dis Prev Rem. 2013; 1 (2): 1-11.

Singhal R, Myneedu VP. Microscopy as a diagnostic tool in pulmonary tuberculosis. Int J Mycobacteriol. 2015; 4(1):1-6.

Gupta S, Prasad V, Bairy I, Muralidharan S. Comparative evaluation of two cold staining methods with the Ziehl-Neelsen method for the diagnosis of tuberculosis. Southeast Asian J Trop Med Public Health. 2009; 40(4):765-9.

Hänscheid T. The future looks bright: low-cost fluorescent microscopes for detection of Mycobacterium tuberculosis and Coccidiae. Trans R Soc Trop Med Hyg. 2008; 102(6):520409 1.

Chang EW, Page AL, Bonnet M. Light-emitting diode fluorescence microscopy for tuberculosis diagnosis: a meta-analysis. Eur Respir J. 2016; 47(3):929-37.

Koch R. Uber bakteriologische forschung. Verhandlungen des X internationalen medizenischen kongresses. Berlin, Germany: August Hirschwald, 1890.

Conti AA, Lippi D, Gensini GF. Tuberculosis: A long fight against it and its current resurgence. Monaldi Archives for Chest Disease - Pulmonary Series. Volume 61, Issue 1, January 2004, pp 71-74.

Besozzi G., Nardini S., Migliori G.B. Tuberculin test and tuberculosis control in a low prevalence country today. Monaldi Archives for Chest Disease. Volume 52, Issue 4, 1997, pp 323. 420

Bazin H. Vaccination: a history. Montrouge, the John Libey Eurotext, 2011.

Koch R. Weitere mitteilungen uber ein heilmittel gegen tuberculose. Dtsch Med Wschr 1891; 101-102.

Nasser Pouyan. The fight against tuberculosis, the loathsome killer. Int.J.Curr.Microbiol.App.Sci. 2015; 4(1): 380-393.

Palmer CE, Bates LE. Tuberculin sensitivity of tuberculous patients. Bull World Health Org. 1952; 7: 171-188.

WHO Tuberculosis Research Office. Further studies of geographic variation in naturally acquired tuberculin sensitivity. Bull World Health Org. 1955; 12:63-83.

Edwards LB, Palmer CE. Identification of the tuberculous-infected by skin tests. Ann NY Acad Sci. 1968; 154: 140-148.

Snider DE Jr. The tuberculin skin test. Am Rev Respir Dis. 1982; 125(3 Pt 2):108-18.

Donelli G., Di Carlo V. La sanità pubblica italiana negli anni a cavallo della Prima Guerra Mondiale. Armando Editore, Roma, 2016. pp 65.

Lenci G. Il pneumotorace artificiale di Carlo Forlanini. Available at: Accessed on 3rd September 2017.

Hjaltested O, Törning K. Clinical aspects of pneumothorax therapy as illustrated by the results obtained in 191 cases of completed treatment. Br J Tuberc. 1939;33.

Mitchell RS. Artificial pneumothorax: a statistical analysis of 557 cases initiated in 1930– 1939 and followed in 1949. I. The influence of clinical findings before induction on early and 441 late results. Am Rev Tuberc.1951;64.

Medical Journal of Sardinian States, 1858.

Cavagnis V. Contro il virus tubercolare e contro la tuberculosi, tentativi sperimentali in atti del Reale Istituto Veneto di Scienze, Lettere e Arti. Venezia, 1886:8.

Grancher JJ, Ledox-Lebard P. Etudes sur la tuberculose experimentale du lapin, in “Arch. De 446 med. Experim. Et d’Anat. Pathol.”, 1891.

Martini M, Paluan F. Edoardo Maragliano (1849-1940): The unfortunate fate of a real pioneer in the fight against tuberculosis. Tuberculosis. 2017; 106:123.

Luca S, Mihaescu T. History of BCG Vaccine. Maedica (Buchar) 2013; 8(1): 53–58.

Martini M, Barberis I, Bragazzi NL, Paluan F. The fight against tuberculosis in the mid nineteenth century: the pivotal contribution of Edoardo Maragliano (1849 - 1940). Advances in experimental medicine and biology. Adv Exp Med Biol. 2017 Nov 21 DOI 10.1007/5584_2017_125.

The Lubeck catastrophe. British Medical Journal. 1931;1:986. Available at: Last access: 15th October 2017.

Martín Montañés C, Gicquel B. New tuberculosis vaccines. Enferm Infecc Microbiol Clin. 2011; 29 Suppl 1:57-62.

Martin C. Tuberculosis vaccines: past, present and future. Curr Opin Pulm Med. 2006; 12(3):186-91.

Orme IM. Vaccine development for tuberculosis: current progress. Drugs. 2013; 73, no.10, 1015–1024.

Fletcher HA, Schrager L. TB vaccine development and the End TB Strategy: importance and current status. Trans R Soc Trop Med Hyg. 2016; 110(4):212-8.

Gengenbacher M, Nieuwenhuizen NE, Kaufmann S. BCG - old workhorse, new skills. Curr Opin Immunol. 2017; 47:8-16.

Kaufmann SH, Weiner J, von Reyn CF. Novel approaches to tuberculosis vaccine development. Int J Infect Dis. 2017; 56:263-267.

Adigun R, Bhimji S. Tuberculosis. StatPearls. Treasure Island (FL): StatPearls Publishing; 2017.

World Health Organisation. Tuberculosis and HIV. 2014. Available at : tb/en/ Accessed on 14.10.2017.

Leutkemeyer A. Tuberculosis and HIV. University of California, San Francisco. Available at : http://www. , accessed on 14.10.2017

World Health Organization – Tuberculosis: a global emergency. Geneva, Switzerland; 1994.

Karo B, Krause G, Castell S, Kollan C, Hamouda O, Haas W; ClinSurv HIV Study Group. Immunological recovery in tuberculosis/HIV co-infected patients on antiretroviral therapy: implication for tuberculosis preventive therapy. BMC Infect Dis. 2017 Jul;17(1):517.

Tiberi S, Carvalho AC, Sulis G, Vaghela D, Rendon A, Mello FC, Rahman A, Matin N, Zumla A, Pontali E. The cursed duet today: Tuberculosis and HIV-coinfection. Presse Med. 2017 Mar; 46(2 Pt 2):e23-e39.

Dye C, Garnett GP, Sleeman K, Williams BG. Prospects for worldwide tuberculosis control under the WHO DOTS strategy. Directly observed short-course therapy. Lancet. 1998 Dec 12;352(9144):1886-91.

Farzianpour F, Kooshad MA. Study of the status of tuberculosis control program based on the implementation of the directly observed treatment short-course strategy (DOTS). Mater Sociomed. 2016 Jul; 28(4):249-252.

Davies, PD. Good news from the WHO(Editorial). IJTLD, Paris, France, Volume 20, Issue 7, 2016 Jul, pp 853.

Cole ST, Brosch R, Parkhill J, Garnier T, Churcher C, Harris D et al. Deciphering the biology of Mycobacterium tuberculosis from the complete genome sequence. Nature. 1998; 393, 537±544.

Choi R, Jeong BH, Koh WJ, Lee SY. Recommendations for Optimizing Tuberculosis Treatment: Therapeutic Drug Monitoring, Pharmacogenetics, and Nutritional Status Considerations. Ann Lab Med. 2017 Mar;37(2):97-107.

Outhred AC, Britton PN, Marais BJ. Drug-resistant tuberculosis − primary transmission and management. Journal of Infection. 2017; 74, S128—S135.

WHO. Drug resistant tuberculosis surveillance&response. Supplement global tuberculosis report 2014. Available at: Last access: 05th October 2017

Manjelievskaia J, Erck D, Piracha S, Schrager L. Drug-resistant TB: deadly, costly and in need of a vaccine. Trans R Soc Trop Med Hyg. 2016 Mar; 110(3):186-91.

Abouda M, Yangui F, Triki M, Kammoun H, Khouani H, Charfi MR. Tuberculosis prevention. Rev Pneumol Clin. 2015; 71(2-3):159-67.

Connell TG, Rangaka MX, Curtis N, Wilkinson RJ. QuantiFERON-TB Gold: state of the art for the diagnosis of tuberculosis infection? Expert Rev Mol Diagn. 2006 Sep;6(5):663-77.

Slim-Saidi L, Mehiri-Zeghal E, Ghariani A, Tritar F. New methods of diagnosis in tuberculosis. Rev Pneumol Clin. 2015;71(2-3):110-21.

Davies, PD. Towards the elimination of tuberculosis and a reduction in chest diseases(Editorial). IJTLD, UK: 2015 Aug, Volume 19, Issue 8, pp. 875.